Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency.

FC Schmalstieg, WJ Leonard… - The Journal of …, 1995 - Am Soc Clin Investig
FC Schmalstieg, WJ Leonard, M Noguchi, M Berg, HE Rudloff, RM Denney, SK Dave…
The Journal of clinical investigation, 1995Am Soc Clin Investig
Clinical and immunologic features of a recently recognized X-linked combined
immunodeficiency disease (XCID) suggested that XCID and X-linked severe combined
immunodeficiency (XSCID) might arise from different genetic defects. The recent discovery
of mutations in the common gamma chain (gamma c) gene, a constituent of several cytokine
receptors, in XSCID provided an opportunity to test directly whether a previously
unrecognized mutation in this same gene was responsible for XCID. The status of X …
Clinical and immunologic features of a recently recognized X-linked combined immunodeficiency disease (XCID) suggested that XCID and X-linked severe combined immunodeficiency (XSCID) might arise from different genetic defects. The recent discovery of mutations in the common gamma chain (gamma c) gene, a constituent of several cytokine receptors, in XSCID provided an opportunity to test directly whether a previously unrecognized mutation in this same gene was responsible for XCID. The status of X chromosome inactivation in blood leukocytes from obligate carriers of XCID was determined from the polymorphic, short tandem repeats (CAG), in the androgen receptor gene, which also contains a methylation-sensitive HpaII site. As in XSCID, X-chromosome inactivation in obligate carriers of XCID was nonrandom in T and B lymphocytes. In addition, X chromosome inactivation in PMNs was variable. Findings from this analysis prompted sequencing of the gamma c gene in this pedigree. A missense mutation in the region coding for the cytoplasmic portion of the gamma c gene was found in three affected males but not in a normal brother. Therefore, this point mutation in the gamma c gene leads to a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID.
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